What is the NCGC Pharmaceutical Collection (NPC)?

The NCGC Pharmaceutical Collection (NPC) is a comprehensive,
publically-accessible collection of approved and
investigational drugs for high-throughput screening that
provides a
valuable resource for both validating new models of
disease and better understanding the molecular basis of
disease pathology and intervention. The NPC has already
generated several useful probes for studying a diverse
cross section of biology, including novel targets and
pathways. NCGC provides access to its set of approved
drugs and bioactives through the Therapeutics for Rare and Neglected Diseases (TRND) program and as part
of the compound collection for the
Tox21
initiative, a collaborative effort
for toxicity screening among several government agencies
including the US Environmental Protection Agency (EPA),
the National Toxicology Program (NTP), the US Food and
Drugs Administration (FDA), and the NCGC. Of
the nearly 2750 small molecular entities (MEs) that have been
approved for clinical use by US (FDA), EU (EMA),
Japanese (NHI), and Canadian (HC) authorities and that
are amenable to HTS screening, we currently possess 2,400
as part of our screening collection.

How do I get access to the NPC?

The NPC resource currently consists of (i) the physical collection suitable
for high throughput screening (HTS) and (ii) the informatics browser and
database. Putting together the physical collection has been surprisingly
challenging in terms of the time and effort required in the informatics,
compound management and synthetic chemistry related activities required
for this endeavor. We provide access to the NPC screening library through
collaboration. Please contact
Ajit Jadhav, Chief, Probe
Development Branch, NCATS
for additional information.

The other half of the NPC resource is the NPC browser. This is a
self-contained software that is actively developed and maintained
by the informatics group to provide electronic access to the NPC content.
The latest version of the NPC browser for various platforms can be
downloaded below. Please let us know if your
platform is not listed. Note that a fairly modern hardware (preferably
with at least 2Gb of memory) is required to run the browser effectively.

Screenshots

What's in the NPC browser?

The primary focus of the NPC browser was initially on approved
molecular entities. In the current version, however, we have expanded
it to include clinical candidates as well as other useful tool molecules.
We hope to eventually reach a steady state whereby new molecular entities
registered with the USAN and INN are automatically incorporated into the browser.

How reliable are the compound records in the NPC browser?

Although we strive to be as accurate as possible, due to the inherent
nature of how chemical structures are defined and represented electronically,
it is simply not possible to have an error-free database. Despite our best
efforts on curation, every structure is suspect until proven otherwise. This
sentiment certainly applies equally to any chemical database.
The NPC resource is—and will continue to be—an ongoing effort as
curation proceeds, new molecular entities are added as they are registered
or approved, and errors are found. This process will benefit enormously from
community feedback, and we encourage users to use the curation mechanism
within the browser to fix and/or report errors.

How can I build my own NPC physical collection?

One of the most challenging efforts in putting together the NPC physical
collection has been that of finding suitable and reliable chemical suppliers.
Furthermore, when drugs cannot be sourced, access to synthetic chemistry
is essential. Additionally, access to good compound management and
analytical chemistry resources is essential in quality control and proper
handling of the drugs collection. Where possible, we have included supplier
names and catalog identifiers in the browser to enable anyone to build their
own physical collection. Given the current collection has been sourced from
a combination of traditional chemical suppliers, specialty collections,
pharmacies and custom synthesis, any serious attempts at replicating the
NPC physical collection will likely to require significant amount of time
and resources.

Has the NPC screening library been characterized analytically?

The NCGC analytical chemistry group is currently generating QC LC/MS
data for all compounds in the NPC physical collection.
Where QC report is available,
a compound record in the NPC browser is marked with the icon
.

How do I cite the NPC resource?

If you make use of the NPC browser and/or database in your research,
please use the following citation to acknowledge the NPC
resource.

Contact

Acknowledgements

The NPC resource has benefited immensely from community feedback
since its initial release. We are particularly grateful
to the following individuals who have generously donated their time
and/or resources in helping us improve the NPC software and database:

Tudor Oprea
, Oleg Ursu,
and Sunset Molecular LLC
graciously donated the drug subset of the WOMBAT database. This
dataset was instrumental in enabling us to validate a large number
of curated structures (i.e., curation of curations so to speak).

Manish Sud was an
early adopter of the NPC resource. His thorough analysis helped us
debugged a number of errors in the software as well as database.

Antony Williams' critical
scrutinies of the compound content revealed numerous errors in the
original version of the database. He also provided valuable feedback
on other issues related to the software and data curation.

We also would like to extend our gratitude to everyone who has
contributed to the curation effort of the NPC database. As a token
of our appreciation, we have created, for each curator, a dedication
badge within the software to acknowledge his/her contribution.

Change Log

Ver.

Date

Changes

1.2.0

Feb 28, 2012

Incorporate additional curated compound records

Improve start-up time

Minor UI changes

Under the hood the codebase is now in sync with the main Tripod
trunk to better support future updates